The objective of the proposed work is to study the regulation of thyroid gland activity by physiological and pathological thyroid stimulators. The fundamental system being used in the study is the use of human thyroid cells in monolayer culture. There are three areas of ongoing investigation. a) Studies are continuing to help elucidate the mechanism and significance of cultured thyroid cell-stimulated prostaglandin E release by human peripheral blood mononuclear cells. It is known that contact between these cell types is necessary for the phenomenon to occur, and the influence of a variety of agents on the process is being studied. b) Because of difficulties experienced in this (and other laboratories) in regard to the binding of radiolabeled TSH to thyroid tissue, studies are ongoing to determine the purity and bioloical activity of the radiolabeled ligand. c) Previous studies from this laboratory have demonstrated desensitization of cultured thyroid cells to a persistent stimulus with thyrotropin (TSH). Ongoing studies are examining the mechanism whereby this effect is produced. In particular the role of ADP-ribosylation in this process is being examined.